ClinVar Miner

Submissions for variant NM_000046.5(ARSB):c.1449A>T (p.Glu483Asp) (rs1064793027)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482506 SCV000564592 likely pathogenic not provided 2016-06-28 criteria provided, single submitter clinical testing A novel E483D missense change likely associated with mucopolysaccharidosis VI (MPSVI) was identified in the ARSB gene. It has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The amino acid change is conservative in that both Glutamic Acid and Aspartic Acid are negatively charged residues; however, this change occurs at a highly conserved position in the ARSB protein and a missense mutation in the neighboring codon (R484G) has been reported previously in association with MPSVI according to the Human Gene Mutation Database. Furthermore, multiple in-silico analysis programs predict that E483D is damaging to the ARSB protein. Therefore, E483D is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded.
Laboratory of Diagnosis and Therapy of Lysosomal Disorders,University of Padova RCV000677488 SCV000802997 uncertain significance Mucopolysaccharidosis type 6 2018-01-01 criteria provided, single submitter curation Very low frequency in GnomAD(PM2)
Invitae RCV000677488 SCV001412579 uncertain significance Mucopolysaccharidosis type 6 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 483 of the ARSB protein (p.Glu483Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with mucopolysaccharidosis (PMID: 22976768). ClinVar contains an entry for this variant (Variation ID: 418018). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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